FDG whole-body PET/CT imaging is a proven technique for the detection of primary and metastatic cancers. It is highly accurate and valuate for cancer staging, re-staging, and monitoring response to therapy for many types of cancers. Despite its success and broad clinical utility, there remains an unmet clinical challenge for the detection of small metastatic cancers that are much smaller than 1 cm. FDG PET/CT has been shown to have limited sensitivity for the detection of such small lesions, in some cases less than 50% of the time. We have developed a novel imaging technology called virtual-pinhole magnifying PET technology that can improve the image resolution of clinical PET/CT scanner to enhance its image resolution and to provide zoom- in images without compromising its body imaging capability. While this is a unique capability, it has not been adopted for clinical whole-body cancer imaging because the location of distant metastasis is often unknown. Therefore, one would not have prior knowledge on where to zoom-in during a whole-body imaging protocol. If on the other hand, one needs to scan the entire body first and then chooses a region of high uncertainty to zoom- in; this technology will require a two-step protocol which will significantly slow down clinical workflow. In this project, we formed a bi-directional partnership between the Washington University School of Medicine (WUSM) and Siemens Molecular Imaging (Siemens MI, Knoxville, TN) to overcome this specific limitation and translate an otherwise novel imaging technology to be suitable for clinical utility. We will jointly develop and validate the Augmented Whole-body Scanning via Magnifying PET (AWSM-PET) technology that will enhance the native image resolution of a PET scanner and is fully compatible with clinical whole-body cancer imaging applications. The added device will not slowdown clinical workflow because the magnifying PET data will be acquired simultaneously with the standard PET data when a patient undergoes a whole-body PET/CT scan. In addition to the standard (native) PET/CT images, AWSM-PET will provide a second set of PET images with higher resolution and counting statistics without additional scan time. This information-rich second data set is expected to further improve the diagnostic accuracy of whole-body PET/CT imaging for the detection of metastatic cancer. Upon completion of this project, we will have developed and validated a new capability that can improve the image resolution and counting statistics of a clinical whole-body PET/CT scanner. If the results of the initial human imaging trial show improvement in diagnostic sensitivity for metastatic cancer detection using a whole- body PET/CT equipped with the AWSM-PET technology, we will seek additional funding to conduct a multi- center clinical trial to fully quantify the improvement in diagnostic accuracy by AWSM-PET technology for the detection of metastatic cancers. The success of this novel in vivo imaging technology will address an unmet challenge of the standard-of-care whole-body PET/CT in detecting small metastatic cancers. The WUSM and Siemens MI partnership will accelerate the delivery of the AWSM-PET technology to end users in nuclear medicine and radiology clinics worldwide. Thus the proposed technology development will have highly significant and broad impact on patients who rely on whole-body PET/CT imaging for accurate diagnosis and optimal management of their diseases.